E-proteins set the threshold for optimal TCF1 expression during αβ T cell development.

Verma, A.; Aylward, B.; Ma, F.; Sherman, C. A.; Chopp, L.; Shinton, S.; Roy, R.; Fahl, S.; Contreras, A.; Koenitzer, B.; Awasthi, P.; Mazan-Mamczarz, K.; De, S.; Ollikainen, N.; Qiu, X.; Bosselut, R.; Sen, R.; Wiest, D.; Sen, J. M.

doi:10.1101/2023.11.06.565822

bioRxiv · 10.1101/2023.11.06.565822

E-proteins set the threshold for optimal TCF1 expression during αβ T cell development.

Verma, A.·Aylward, B.·Ma, F.·Sherman, C. A.·Chopp, L.·Shinton, S.·Roy, R.·Fahl, S.·Contreras, A.·Koenitzer, B.·Awasthi, P.·Mazan-Mamczarz, K.·De, S.·Ollikainen, N.·Qiu, X.·Bosselut, R.·Sen, R.·Wiest, D.·Sen, J. M.

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Abstract

Expression of T Cell Factor-1 (TCF1), encoded by Tcf7, regulates lineage fate decisions during T cell development. Here we demonstrate that E-proteins control the threshold of TCF1 expression required for development of T cells. E-proteins bind to five elements (EPEs) in the Tcf7 locus. The third element, EPE3, interacts directly with Tcf7 promoter in Hi-ChIP analyses, suggesting it is an active enhancer. CRISPR-ablation of EPE3 reduces TCF1 protein expression in precursor thymocytes by 2-fold and dramatically impairs development of {beta} and {gamma}{delta} T cells. Single cell gene expression analysis identified differentiation blocks at multiple CD4-CD8- stages and subsequent transition to CD4+CD8+ stage. These data identify E-proteins and EPE3 as critical for the optimal TCF1 expression required for T cell development.

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Verma, A., Aylward, B., Ma, F., Sherman, C. A., Chopp, L., Shinton, S., Roy, R., Fahl, S., Contreras, A., Koenitzer, B., Awasthi, P., Mazan-Mamczarz, K., De, S., Ollikainen, N., Qiu, X., Bosselut, R., Sen, R., Wiest, D., Sen, J. M.. 2023-11-06. E-proteins set the threshold for optimal TCF1 expression during αβ T cell development.. https://doi.org/10.1101/2023.11.06.565822

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